Previous studies of shock injury have been primarily confined to classical physiological data. New and improved methodology will now permit detailed study of changes in cellular function, including membrane and transport functions. Profound alterations in the volume and composition of extracellular fluid and electrolytes in response to shock can be measured. Recent studies have indicated the usefulness of direct in vivo measurements of transmembrane potential by intracellular microelectrodes as a determinant of cellular injury. Techniques for measuring the extracellular fluid composition by direct aspiration in vivo have also been developed. Additionally, action potentials in skeletal muscle in vivo in primates are being used. Using these techniques, reversible and irreversible alterations in cellular function are being studied. Various forms of shock can be shown to depolarize single muscle cells, interfere with active sodium and potassium transport and allow passive redistribution of chloride between intracellular and extracellular compartments. Similar disturbances are being measured in other cells including hepatic cells. Studies will be extended to other organ cells. Direct intracellular measurement of pH in vivo has also been developed, indicating that H ion is in instantaneous electrochemical equilibrium between bulk phase intracellular compartment and the extracellular compartment. Studies are being conducted to ascertain where this fundamental relationship is maintained in the low flow states. Using these more sensitive indicators of cellular function, basic mechanisms can now be investigated. These include the cellular response to different forms of shock including hypovolemic, septic, thermal, and crush injury. Measurement of these direct parameters will also allow cellular definition of response to various types and quantities of therapy. Consequently, therapeutic effectiveness should be discernible on a more rational and critical basis.